Keratitis caused by herpes simplex virus (HSV) is the single most frequent cause of corneal opacities in developed countries. The disease is characterized by a cheesy white cellular infiltrate and may result in permanent eye damage and blindness. Most evidence suggests that the host response to viral antigens in responsible for the opacities, in which the most important long term factor is stromal carring. Although the disease can persist for long periods of time, infectious virus is rarely isolated. However, studies have related that viral antigens persist in the diseased eye. The overall purpose of the proposed study will be to locate and identify viral antigens associated with stromal disease and to determine their role, as well as that of infectious virus, in initiating and maintaining cellular infiltrates. Stromal disease will be produced by injecting infectious virus (RE strain) into the corneas of New Zealand white rabbits, a model which closely mimics stromal disease in humans. Other objectives will be (1) to determine if Fc receptors are formed on cells infected during stromal disease and if they are associated with cells responding to infection, (2) to study the replication of HSV in monolayer cultures of epithelial, stromal, and endothelial corneal cells, (3) to identify immune effector cells reactive with corneal cells infected with HSV, and (4) to determine the ability of HSV to replicate in, and effect the functions of, immune effector cells. To identify specific antigens in stromal disease, we will use antipolypeptide sera prepared from HSV proteins separated by polyacrylamide gel electrophoresis. Antisera will be labeled with fluorescein, 125I, and ferritin and reacted with antigens in cryostat sections for examination by light, fluorescence, and electron microscopy. The course of antigen production and persistence will be correlated with histopathological findings and manifestations of disease.